Thyroid hormone (TH) has diverse effects on mammals, including effects on the neonatal and adult brain. In the developing animal, thyroid hormone regulates various events such as neuronal processing, glial cell proliferation, myelination, and neurotransmitter enzyme synthesis. The metabolically active form of thyroid hormone, 3, 5, 3′-triiodothyronine (T3), acts by binding to two receptors; TRα1 and TRβ1. These two receptors are encoded by the c-erbAα locus. Two truncated receptor transcripts have been identified that are also transcribed from the c-erbAα locus; ΔTRα1 and ΔTRα2 (Chassande et al., 1997, Mol. Endocrinol. 11:1278-1290). Neither truncated receptor has a DNA binding region and ΔTRα1 has been shown to antagonize T3-induced transcriptional activation.
Type II iodothyronine 5′-deiodinase (D2) is the key enzyme in the pathway that mediates the conversion of intracellular thyroxine (T4) to 3, 5, 3′-triiodothyronine (T3). D2 concentration can be mediated by thyroid hormone concentration and is regulated by enzyme inactivation. The D2 activity appears to be more sensitive to T4 than T3. The degradation of the enzyme is energy-dependent and apparently requires the structural integrity of the actin cytoskeleton, i.e., is regulated at least in part by actin-based endocytosis. p29 is the substrate binding subunit of D2. T4 induces inactivation of D2 and initiates the binding of p29 to F-actin. The bound p29 is transported to an endosomal pool followed by dissociation of the F-actin-p29 complex (Farwell et al., 1993, J. Biol. Chem. 268: 5055-5062).